1. Field
One or more embodiments relate to a bacterium that produces monophosphoryl lipid A (MLA), and a method of producing MLA by using the bacterium.
2. Description of the Related Art
Lipopolysaccharides (LPS) are one of the components of the outer membrane surrounding peptidoglycan of Gram-negative bacteria. LPS are molecules containing lipid A and a variety of polysaccharides conjugated with the lipid A by a covalent bond. Among the components of LPS, Lipid A, which is also known as endotoxin, is held responsible for the toxicity of Gram-negative bacteria.
Lipid A is a very potent stimulant of the immune system, activating cells (for example, monocytes or macrophages) at picogram per milliliter quantitites. Lipid A, derivatives of lipid A, or varients of lipid A can be used as, for example, components of vaccines such as adjuvants. Monophosphoryl lipid A (MLA) is used as adjuvants and used for allergen-specific immunotherapy and immunotherapy of cancer, or also effective in prevention and treatment of dementia. Furthermore, among MLA, hexa-acylated-monophosphoryl lipid A (hexa-acylated MLA), penta-acylated-monophosphoryl lipid A (penta-acylated MLA), and 3-O-desacyl-4′-monophosphoryl lipid A (3D-MLA) are effective in the above-mentioned use. Lipid A is a lipid component found in the membrane of Gram-negative bacteria, such as Escherichia coli. Lipid A found in the membrane conjugates to sugars, such as 2-keto-3-deoxy-D-manno-octulosonate (Kdo). Therefore, in order to obtain lipid A in a free form, it should be isolated from the other components of LPS. For example, LPS can be extracted from bacterial membranes, heated in the presence of acids so as to remove Kdo, and a 1-phosphate group, thereby obtaining Lipid A; or MLA can be synthesized by chemical processing. However, these methods have drawbacks in that they are complicated in steps of the processes, with a low yield.
Therefore, there is a need to develop a method of producing MLA and derivatives thereof, which is simpler than the conventional methods, without acid hydrolysis.